Emergency department staff compassion is associated with lower fear of enacted stigma among patients with opioid use disorder.

OBJECTIVES: Fear of enacted stigma (fear of discrimination or being treated unfairly) is associated with decreased health care-seeking behaviors among patients with opioid use disorder (OUD). We sought to describe the prevalence of fear of enacted stigma among patients presenting to the emergency department (ED) with OUD and to test whether experiencing greater compassion from ED staff is associated with lower fear of enacted stigma. METHODS: We conducted a cross-sectional study in the ED of an academic medical center between February and August 2023. We included adult patients with OUD presenting to the ED and assessed patient experience of compassion from ED staff using a previously validated 5-item compassion measure (score range 5-20). The primary outcome measure was fear of enacted stigma in the ED, measured using the validated 9-item subscale of the Substance Abuse Self-Stigma Scale (score range 9-45). RESULTS: Of the 116 subjects enrolled, 97% (95% confidence interval [CI] 91%-99%) reported some degree of stigma, with a median (interquartile range) score of 23 (16-31). In a multivariable model adjusting for potential confounders, patient experience of greater ED compassion was independently associated with lower fear of enacted stigma, ß = -0.66 (95% CI -1.03 to -0.29), suggesting that every 1-point increase in the 5-item compassion measure score is associated with a 0.66-point decrease in the fear of enacted stigma score. CONCLUSIONS: Among ED patients with OUD, fear of enacted stigma is common. Patient experience of compassion from ED staff is associated with lower fear of enacted stigma. Future research is warranted to test if interventions aimed at increasing compassion from ED staff reduce patient fear of enacted stigma among patients with OUD.

Posttraumatic stress disorder symptoms after respiratory and cardiovascular emergencies predict risk of hospital readmission: A prospective cohort study.

BACKGROUND: Twenty-five percent of patients presenting to the emergency department (ED) for a respiratory or cardiovascular medical emergency develop clinically significant posttraumatic stress disorder (PTSD) symptoms. It is possible that development of PTSD symptoms in this cohort is associated with subsequent adverse physical health events. Our objective was to test whether clinically significant PTSD symptoms 30 days postdischarge are associated with increased risk for hospital readmission within 24 months after discharge among patients presenting to the ED for a respiratory or cardiovascular emergency. METHODS: This was a prospective cohort study conducted between January 1, 2018, and December 31, 2020, at a U.S. academic medical center, including adult patients presenting with acute respiratory failure or cardiovascular instability requiring a potentially life-sustaining intervention in the ED. PTSD symptoms 30 days postdischarge were measured using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders-5. The primary outcome was all-cause hospital readmission over the subsequent 24 months after hospital discharge from the index ED visit. RESULTS: Of the 99 patients included, 73% (95% confidence interval [CI] = 63% to 81%) had a hospital readmission within 24 months. In a multivariable Cox proportional hazards model adjusting for potential confounders (e.g., age, severity of illness during index ED visit, preexisting comorbid conditions) presence of clinically significant PTSD symptoms at 30 days was independently associated with increased risk for all-cause hospital readmission at 24 months (hazards ratio = 2.19, 95% CI = 1.30 to 3.69). These results remained statistically significant across multiple sensitivity analyses. CONCLUSIONS: Hospital readmission is common among survivors of acute respiratory failure and cardiovascular instability, and PTSD symptoms 30 days postdischarge are an independent predictor of hospital readmission. Survivors of medical emergencies may warrant follow-up evaluation for PTSD symptoms, and future research is warranted to better understand the relationship between psychological trauma and hospital readmission.

Validation of a 5-Item Tool to Measure Patient Assessment of Clinician Compassion in Hospitals.

BACKGROUND: We previously validated a 5-item compassion measure to assess patient experience of clinician compassion in the outpatient setting. However, currently, there is no validated and feasible method for health care systems to measure patient experience of clinician compassion in the inpatient setting across multiple hospitals. OBJECTIVE: To test if the 5-item compassion measure can validly and distinctly measure patient assessment of physician and nurse compassion in the inpatient setting. DESIGN: Cross-sectional study between July 1 and July 31, 2020, in a US health care network of 91 community hospitals across 16 states consisting of approximately 15,000 beds. PATIENTS: Adult patients who had an inpatient hospital stay and completed the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. MEASUREMENTS: We adapted the original 5-item compassion measure to be specific for physicians, as well as for nurses. We disseminated both measures with the HCAHPS survey and used confirmatory factor analysis for validity testing. We tested reliability using Cronbach's alpha, as well as convergent validity with patient assessment of physician and nursing communication and overall hospital rating questions from HCAHPS. RESULTS: We analyzed 4756 patient responses. Confirmatory factor analysis found good fit for two distinct constructs (i.e., physician and nurse compassion). Both measures demonstrated good internal consistency (alpha > 0.90) and good convergent validity but reflected a construct (compassionate care) distinct from what is currently captured in HCAHPS. CONCLUSION: We validated two 5-item tools that can distinctly measure patient experience of physician and nurse compassion for use in the inpatient hospital setting in conjunction with HCAHPS.

Preconsultation compassion intervention to reduce anxiety among patients referred to a cancer center: protocol for a randomised control trial.

INTRODUCTION: Patients diagnosed with cancer commonly have a high degree of anxiety during an initial oncology consultation, which may interfere with a patient's ability to retain information required to make informed treatment decisions. A previous study randomised breast cancer survivors (volunteers) to view either (a) a brief video depicting a standard initial consultation from an oncologist or (b) an identical consultation with the addition of compassionate statements from the oncologist, and found the compassionate statements reduced anxiety among the volunteers. However, while compassionate statements reduced anxiety during simulation, it is currently unknown whether watching a video containing compassionate statements from an oncologist prior to an initial oncology consultation will reduce anxiety among patients referred to a cancer centre. The aim of this randomised control trial is to test whether watching a brief video containing compassionate statements from an oncologist, compared with watching a standard introduction video, prior to an initial oncology consultation will reduce the degree of anxiety among patients referred to a cancer centre. METHODS AND ANALYSIS: This is a prospective, randomised controlled clinical trial at an academic cancer centre. We will enrol adult patients scheduled for an initial oncology consultation. Subjects will be randomly assigned to receive a standard introduction video or enhanced compassion video for viewing prior to the initial oncology consultation. On arrival to the cancer centre, we will measure anxiety severity using the Hospital Anxiety and Depression Scale (HADS). The HADS has two 7-item subscales (HADS anxiety and HADS depression) and is well-validated among oncology patients. We will use Wilcoxon rank-sum test to test for a difference in the HADS subscales between the two video groups. ETHICS AND DISSEMINATION: The Cooper University Hospital Institutional Review Board approved this study. The results from this randomised control trial will be submitted for publication to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04503681.

Socioeconomic, racial and ethnic differences in patient experience of clinician empathy: Results of a systematic review and meta-analysis.

INTRODUCTION: Empathy is essential for high quality health care. Health care disparities may reflect a systemic lack of empathy for disadvantaged people; however, few data exist on disparities in patient experience of empathy during face-to-face health care encounters with individual clinicians. We systematically analyzed the literature to test if socioeconomic status (SES) and race/ethnicity disparities exist in patient-reported experience of clinician empathy. METHODS: Using a published protocol, we searched Ovid MEDLINE, PubMed, CINAHL, EMBASE, CENTRAL and PsychINFO for studies using the Consultation and Relational Empathy (CARE) Measure, which to date is the most commonly used and well-validated methodology for measuring clinician empathy from the patient perspective. We included studies containing CARE Measure data stratified by SES and/or race/ethnicity. We contacted authors to request stratified data, when necessary. We performed quantitative meta-analyses using random effects models to test for empathy differences by SES and race/ethnicity. RESULTS: Eighteen studies (n = 9,708 patients) were included. We found that, compared to patients whose SES was not low, low SES patients experienced lower empathy from clinicians (mean difference = -0.87 [95% confidence interval -1.72 to -0.02]). Compared to white patients, empathy scores were numerically lower for patients of multiple race/ethnicity groups (Black/African American, Asian, Native American, and all non-whites combined) but none of these differences reached statistical significance. CONCLUSION: These data suggest an empathy gap may exist for patients with low SES. More research is needed to further test for SES and race/ethnicity disparities in clinician empathy and help promote health care equity. TRIAL REGISTRATION: Registration (PROSPERO): CRD42019142809.

Effects of hypercapnia in sepsis: A scoping review of clinical and pre-clinical data.

BACKGROUND: Perform a scoping review of (1) pre-clinical studies testing the physiological effects of higher PaCO2 levels in the setting of sepsis models and (2) clinical investigations testing the effects of hypercapnia on clinical outcomes in mechanically ventilated patients with sepsis. METHODS: We performed a search of CENTRAL, PUBMED, CINAHL, and EMBASE. Study inclusion criteria for pre-clinical studies were: (1) bacterial sepsis model (2) measurement of PaCO2 , and (3) comparison of outcome measure between different PaCO2 levels. Inclusion criteria for clinical studies were: (1) diagnosis of sepsis, (2) receiving invasive mechanical ventilation, (3) measurement of PaCO2 , and (4) comparison of outcomes between different PaCO2 levels. We performed a qualitative analysis to collate and summarize the physiological and clinical effects of hypercapnia according to the recommended methodology from the Cochrane Handbook. RESULTS: Fifteen pre-clinical and nine clinical studies were included. Among pre-clinical studies, the individual studies found higher PaCO2 augments tissue blood flow and oxygenation, and attenuates inflammation and lung injury; however, all pre-clinical studies were found to have some degree of risk of bias. Six of the nine clinical studies were deemed to be good quality. Among clinical studies hypercapnia was associated with increased cerebral perfusion and oxygenation; however, there were conflicting results testing the association between hypercapnia and mortality. CONCLUSION: While individual pre-clinical studies identified potential mechanisms by which changes in PaCO2 levels could affect pathophysiology in sepsis, there is a paucity of clinical data as to the optimal PaCO2 range, demonstrating a need for future research. REGISTRATION: PROSPERO number CRD42018086703.

Racial and socioeconomic disparities in patient experience of clinician empathy: a protocol for systematic review and meta-analysis.

INTRODUCTION: Clinician empathy is a vital component of high-quality healthcare. Healthcare disparities may reflect a societal lack of empathy for disadvantaged persons in general, and recent research suggests that socioeconomic disparities exist in patient satisfaction with clinicians. However, it is currently unclear if there are disparities in patient experience of empathy from clinicians. Our objective is to systematically analyse the scientific literature to test the hypothesis that racial and socioeconomic status (SES) disparities exist in patient-reported experience of clinician empathy. METHODS AND ANALYSIS: In accordance with published methodological guidelines for conducting a systematic review, we will analyse studies reporting patient assessment of clinician empathy using the Consultation and Relational Empathy (CARE) measure, which to date is the most commonly used and well-validated methodology in clinical research for measuring clinician empathy from the patient's perspective. We will use a standardised data collection template and assess study quality (risk of bias) using the Newcastle-Ottawa Scale. We will abstract data for the CARE measure stratified by race and SES, and we will contact the corresponding authors to obtain stratified data by race/SES if not reported in the original manuscript. Where appropriate, we will pool the data and perform quantitative meta-analysis to test if non-white (compared to white) patients and low SES (compared to high SES) patients report lower scores for clinician empathy. ETHICS AND DISSEMINATION: No individual patient-level data will be collected and thus the proposed systematic review does not require ethical approval. This systematic review will test if racial and SES differences exist in patient experience of clinician empathy, and will inform future research to help promote healthcare equity. PROSPERO REGISTRATION NUMBER: CRD42019142809.

Association Between Perceived Threat and the Development of Posttraumatic Stress Disorder Symptoms in Patients With Life-threatening Medical Emergencies.

BACKGROUND: Our objectives were to test whether during a potentially life-threatening medical emergency, perceived threat (a patient's sense of life endangerment) in the emergency department (ED) is common and associated with the subsequent development of posttraumatic stress disorder (PTSD) symptoms. METHODS: This study was an ED-based prospective cohort study in an academic hospital. We included adult patients requiring acute intervention in the ED for resuscitation of a potentially life-threatening medical emergency, defined as respiratory or cardiovascular instability. We measured patient-perceived threat in the ED using a validated patient self-assessment measure (score range = 0 to 21, with higher scores indicating greater perceived threat). We performed blinded assessment of PTSD symptoms 30 days after discharge using the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5). RESULTS: Ninety-nine of 113 (88%) patients completed follow-up, with 98% reporting some degree of perceived threat, median (interquartile range [IQR]) perceived threat score 12 (6 to 17), and 72% reported PTSD symptoms in relation to their ED visit (median [IQR] PCL-5 score = 7 [0 to 30]). Patients with respiratory instability had higher median (IQR) perceived threat scores (16 [9 to 18] vs. 9 [6 to 14)] and PCL-5 scores (10 [2 to 40] vs. 3 [0 to 17]) compared to patients without respiratory instability. In a multivariable linear regression model adjusting for potential confounders, greater perceived threat in the ED was independently associated with higher PCL-5 scores (ß = 0.79, 95% confidence interval [CI] = 0.15 to 1.42). Among the individual perceived threat items, the feeling of helplessness during resuscitation had the strongest association with PCL-5 score (ß = 5.24, 95% CI = 2.29 to 8.18). CONCLUSIONS: Perceived threat during potentially life-threatening emergencies is common and independently associated with development of PTSD symptoms. Additional research to test whether reduction of perceived threat in the ED attenuates the development of PTSD symptoms following potentially life-threatening emergencies is warranted.

Validation of a 5-item tool to measure patient assessment of clinician compassion in the emergency department.

BACKGROUND: To test if the 5-item compassion measure (a tool previously validated in the outpatient setting to measure patient assessment of clinician compassion) is a valid and reliable tool to quantify a distinct construct (i.e. clinical compassion) among patients evaluated in the emergency department (ED). METHODS: Cross-sectional study conducted in three academic emergency departments in the U.S. between November 2018 and April 2019. We enrolled adult patients who were evaluated in the EDs of the participating institutions and administered the 5-item compassion measure after completion of care in the ED. Validity testing was performed using confirmatory factor analysis. Cronbach's alpha was used to test reliability. Convergent validity with patient assessment of overall satisfaction questions was tested using Spearman correlation coefficients and we tested if the 5-item compassion measure assessed a construct distinct from overall patient satisfaction using confirmatory factor analysis. RESULTS: We analyzed 866 patient responses. Confirmatory factor analysis found all five items loaded well on a single construct and our model was found to have good fit. Reliability was excellent (Cronbach's alpha = 0.93) among the entire cohort. These results remained consistent on sub-analyses stratified by individual institutions. The 5-item compassion measure had moderate correlation with overall patient satisfaction (r = 0.66) and patient recommendation of the ED to friends and family (r = 0.57), but reflected a patient experience domain (i.e. compassionate care) distinctly different from patient satisfaction. CONCLUSIONS: The 5-item compassion measure is a valid and reliable tool to measure patient assessment of clinical compassion in the ED.

Curricula for empathy and compassion training in medical education: A systematic review.

BACKGROUND: Empathy and compassion are vital components of health care quality; however, physicians frequently miss opportunities for empathy and compassion in patient care. Despite evidence that empathy and compassion training can be effective, the specific behaviors that should be taught remain unclear. We synthesized the biomedical literature on empathy and compassion training in medical education to find the specific curricula components (skills and behaviors) demonstrated to be effective. METHODS: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL using a previously published comprehensive search strategy. We screened reference lists of the articles meeting inclusion criteria to identify additional studies for potential inclusion. Study inclusion criteria were: (1) intervention arm in which subjects underwent an educational curriculum aimed at enhancing empathy and/or compassion; (2) clearly defined control arm in which subjects did not receive the curriculum; (3) curriculum was tested on physicians (or physicians-in-training); and (4) outcome measure assessing the effect of the curriculum on physician empathy and/or compassion. We performed a qualitative analysis to collate and tabulate effects of tested curricula according to recommended methodology from the Cochrane Handbook. We used the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: Fifty-two studies (total n = 5,316) met inclusion criteria. Most (75%) studies found that the tested curricula improved physician empathy and/or compassion on at least one outcome measure. We identified the following key behaviors to be effective: (1) sitting (versus standing) during the interview; (2) detecting patients' non-verbal cues of emotion; (3) recognizing and responding to opportunities for compassion; (4) non-verbal communication of caring (e.g. eye contact); and (5) verbal statements of acknowledgement, validation, and support. These behaviors were found to improve patient perception of physician empathy and/or compassion. CONCLUSION: Evidence suggests that training can enhance physician empathy and compassion. Training curricula should incorporate the specific behaviors identified in this report.

Development and Validation of a Tool to Measure Patient Assessment of Clinical Compassion.

Importance: Clinician compassion is a vital element of health care quality. Currently, there appears to be no validated and feasible method for health care organizations to measure patient assessment of clinician compassion on a large scale. Objective: To develop and validate a tool for measuring patient assessment of clinician compassion that can be used in conjunction with the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) survey. Design, Setting, and Participants: This prospective cohort study took place from June 1 to August 30, 2018, at a US academic health care system among a pilot cohort consisting of 3325 adult patients and a validation cohort consisting of 3483 adult patients, both of whom had an outpatient clinic visit and completed the CG-CAHPS survey. Main Outcomes and Measurements: After a comprehensive literature review, 12 candidate survey items were developed. Face and construct validity were performed. Candidate items were disseminated to patients in conjunction with the CG-CAHPS survey in a series of 2 studies: (1) exploratory factor analysis in one cohort to determine the factor structure and the most parsimonious set of items; and (2) validity testing in a second cohort using confirmatory factor analysis. Reliability was tested using Cronbach α. Convergent validity was tested with patient assessment of clinician communication and overall satisfaction questions from CG-CAHPS survey. Results: Overall, 6493 patient responses were analyzed. The mean (SD) age was 60 (15) years, 4239 patients (65.3%) were women, and 5079 (78.2%) were white. Exploratory factor analyses identified a 5-item compassion measure to be the most parsimonious. Confirmatory factor analyses found good fit. The compassion measure demonstrated good internal consistency (α = 0.94) and convergent validity (clinician communication: ρ = 0.44; overall satisfaction: ρ = 0.52) but reflected a patient experience domain (compassionate care) distinct from what is currently captured in the CG-CAHPS survey. Conclusions and Relevance: A simple 5-item tool to measure patient assessment of clinician compassion was developed and validated for use in conjunction with CG-CAHPS survey.

Healthcare provider compassion is associated with lower PTSD symptoms among patients with life-threatening medical emergencies: a prospective cohort study.

PURPOSE: We tested the hypothesis that, during a life-threatening medical emergency, patient perception of healthcare provider (HCP) compassion is associated with the subsequent development of post-traumatic stress disorder (PTSD) symptoms. METHODS: Prospective cohort study in the emergency department (ED) of an urban academic medical center. We included adult patients presenting with a life-threatening medical emergency, defined as respiratory or cardiovascular instability requiring a potentially life-sustaining intervention in the ED. We measured patient perception of HCP compassion in the ED using the Consultation and Relational Empathy (CARE) measure, a validated 40-point scale. Blinded to clinical outcomes (including the CARE measure), we assessed PTSD symptoms 1 month post-discharge using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders-5. RESULTS: Of the 99/113 (88%) patients who completed follow-up, 25% (95% CI 17-35%) had PTSD symptoms at 1 month. In a multivariable model adjusting for potential confounders (e.g. severity of illness score in ED, need for intensive care unit admission, ED overcrowding, and family member emotional support in the ED), patient perception of greater HCP compassion in the ED was independently associated with lower PTSD symptoms at 1 month [odds ratio 0.93 (95% CI 0.89-0.98)]. A one-point increase in the CARE measure was associated with a 7% decrease in the odds of developing PTSD symptoms. CONCLUSIONS: PTSD symptoms are common among ED patients with life-threatening medical emergencies. Patient perception of greater HCP compassion during the emergency is independently associated with lower risk of developing PTSD symptoms.

Partial pressure of arterial carbon dioxide after resuscitation from cardiac arrest and neurological outcome: A prospective multi-center protocol-directed cohort study.

AIMS: Partial pressure of arterial carbon dioxide (PaCO2) is a regulator of cerebral blood flow after brain injury. We sought to test the association between PaCO2 after resuscitation from cardiac arrest and neurological outcome. METHODS: A prospective protocol-directed cohort study across six hospitals. INCLUSION CRITERIA: age ≥18, non-traumatic cardiac arrest, mechanically ventilated after return of spontaneous circulation (ROSC), and receipt of targeted temperature management. Per protocol, PaCO2 was measured by arterial blood gas analyses at one and six hours after ROSC. We determined the mean PaCO2 over this initial six hours after ROSC. The primary outcome was good neurological function at hospital discharge, defined a priori as a modified Rankin Scale ≤3. Multivariable Poisson regression analysis was used to test the association between PaCO2 and neurological outcome. RESULTS: Of the 280 patients included, the median (interquartile range) PaCO2 was 44 (37-52) mmHg and 30% had good neurological function. We found mean PaCO2 had a quadratic (inverted "U" shaped) association with good neurological outcome, with a mean PaCO2 of 68 mmHg having the highest predictive probability of good neurological outcome, and worse neurological outcome at higher and lower PaCO2. Presence of metabolic acidosis attenuated the association between PaCO2 and good neurological outcome, with a PaCO2 of 51 mmHg having the highest predictive probability of good neurological outcome among patients with metabolic acidosis. CONCLUSION: PaCO2 has a "U" shaped association with neurological outcome, with mild to moderate hypercapnia having the highest probability of good neurological outcome.

Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study.

OBJECTIVES: Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated postresuscitation mean arterial blood pressure is associated with neurologic outcome. DESIGN: Preplanned analysis of a prospective cohort study. SETTING: Six academic hospitals in the United States. PATIENTS: Adult, nontraumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation. INTERVENTIONS: Mean arterial blood pressure was measured noninvasively after return of spontaneous circulation and every hour during the initial 6 hours after return of spontaneous circulation. MEASURES AND MAIN RESULTS: We calculated the mean arterial blood pressure and a priori dichotomized subjects into two groups: mean arterial blood pressure 70-90 and greater than 90 mm Hg. The primary outcome was good neurologic function, defined as a modified Rankin Scale less than or equal to 3. The modified Rankin Scale was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean arterial blood pressure greater than 90 mm Hg. Good neurologic function at hospital discharge occurred in 30% of patients in the entire cohort and was significantly higher in patients with a mean arterial blood pressure greater than 90 mm Hg (42%) as compared with mean arterial blood pressure 70-90 mm Hg (15%) (absolute risk difference, 27%; 95% CI, 17-37%). In a multivariable Poisson regression model adjusting for potential confounders, mean arterial blood pressure greater than 90 mm Hg was associated with good neurologic function (adjusted relative risk, 2.46; 95% CI; 2.09-2.88). Over ascending ranges of mean arterial blood pressure, there was a dose-response increase in probability of good neurologic outcome, with mean arterial blood pressure greater than 110 mm Hg having the strongest association (adjusted relative risk, 2.97; 95% CI, 1.86-4.76). CONCLUSIONS: Elevated blood pressure during the initial 6 hours after resuscitation from cardiac arrest was independently associated with good neurologic function at hospital discharge. Further investigation is warranted to determine if targeting an elevated mean arterial blood pressure would improve neurologic outcome after cardiac arrest.

Microcirculatory perfusion disturbances in septic shock: results from the ProCESS trial.

BACKGROUND: We sought to determine the effects of alternative resuscitation strategies on microcirculatory perfusion and examine any association between microcirculatory perfusion and mortality in sepsis. METHODS: This was a prospective, formally designed substudy of participants in the Protocolized Care in Early Septic Shock (ProCESS) trial. We recruited from six sites with the equipment and training to perform these study procedures. All subjects were adults with septic shock, and each was assigned to alternative resuscitation strategies. The two main analyses assessed (1) the impact of resuscitation strategies on microcirculatory perfusion parameters and (2) the association of microcirculatory perfusion with 60-day in-hospital mortality. We measured sublingual microcirculatory perfusion using sidestream dark field in vivo video microscopy at the completion of the 6-h ProCESS resuscitation protocol and then again at 24 and 72 h. RESULTS: We enrolled 207 subjects (demographics were similar to the overall ProCESS cohort) and observed 40 (19.3%) deaths. There were no differences in average perfusion characteristics between treatment arms. Analyzing the relationship between microcirculatory perfusion and mortality, we found an association between vascular density parameters and mortality. Total vascular density (beta = 0.006, p < 0.003), perfused vascular density (beta = 0.005, p < 0.04), and De Backer score (beta = 0.009, p < 0.01) were higher overall in survivors in a generalized estimating equation model, and this association was significant at the 72-h time point (p < 0.05 for each parameter). CONCLUSIONS: Microcirculatory perfusion did not differ between three early septic shock treatment arms. We found an association between microcirculatory perfusion parameters of vascular density at 72 h and mortality. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00510835 . Registered on August 2, 2007.

Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial.

Importance: Polymyxin B hemoperfusion reduces blood endotoxin levels in sepsis. Endotoxin activity can be measured in blood with a rapid assay. Treating patients with septic shock and elevated endotoxin activity using polymyxin B hemoperfusion may improve clinical outcomes. Objective: To test whether adding polymyxin B hemoperfusion to conventional medical therapy improves survival compared with conventional therapy alone among patients with septic shock and high endotoxin activity. Design, Setting, and Participants: Multicenter, randomized clinical trial involving 450 adult critically ill patients with septic shock and an endotoxin activity assay level of 0.60 or higher enrolled between September 2010 and June 2016 at 55 tertiary hospitals in North America. Last follow-up was June 2017. Interventions: Two polymyxin B hemoperfusion treatments (90-120 minutes) plus standard therapy completed within 24 hours of enrollment (n = 224 patients) or sham hemoperfusion plus standard therapy (n = 226 patients). Main Outcomes and Measures: The primary outcome was mortality at 28 days among all patients randomized (all participants) and among patients randomized with a multiple organ dysfunction score (MODS) of more than 9. Results: Among 450 eligible enrolled patients (mean age, 59.8 years; 177 [39.3%] women; mean APACHE II score 29.4 [range, 0-71 with higher scores indicating greater severity), 449 (99.8%) completed the study. Polymyxin B hemoperfusion was not associated with a significant difference in mortality at 28 days among all participants (treatment group, 84 of 223 [37.7%] vs sham group 78 of 226 [34.5%]; risk difference [RD], 3.2%; 95% CI, -5.7% to 12.0%; relative risk [RR], 1.09; 95% CI, 0.85-1.39; P = .49) or in the population with a MODS of more than 9 (treatment group, 65 of 146 [44.5%] vs sham, 65 of 148 [43.9%]; RD, 0.6%; 95% CI, -10.8% to 11.9%; RR, 1.01; 95% CI, 0.78-1.31; P = .92). Overall, 264 serious adverse events were reported (65.1% treatment group vs 57.3% sham group). The most frequent serious adverse events were worsening of sepsis (10.8% treatment group vs 9.1% sham group) and worsening of septic shock (6.6% treatment group vs 7.7% sham group). Conclusions and Relevance: Among patients with septic shock and high endotoxin activity, polymyxin B hemoperfusion treatment plus conventional medical therapy compared with sham treatment plus conventional medical therapy did not reduce mortality at 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT01046669.

Effects of hypercapnia in sepsis: protocol for a systematic review of clinical and preclinical data.

BACKGROUND: Respiratory failure requiring mechanical ventilation is a common manifestation of end-organ damage among patients with sepsis and has a high morbidity and mortality rate, as well as substantial associated treatment costs. Considering the burden of this condition, there is great need to identify novel, pragmatic therapies to improve outcomes in this population. Hypercapnia has shown benefits in several different ex vivo and in vivo models of lung injury. However, it is currently unclear if hypercapnia can confer clinical benefit among patients with sepsis. The objective of this systematic review is to collate the biomedical literature of preclinical and clinical studies testing the effects of higher PaCO2 levels in the setting of sepsis. METHODS: We will perform a qualitative systematic review of preclinical and clinical studies evaluating the effects of hypercapnia in sepsis. We will search CENTRAL, PubMed, CINAHL, and EMBASE using a comprehensive strategy. We will screen the reference lists of the articles we select for inclusion to identify additional studies for potential inclusion. Two independent reviewers will review all search results. Upon inclusion of articles, we will extract data using a standardized form. We will use tables to describe the study type, population included, exposure and control groups, outcome measures, and effects of exposure on outcome measures compared to controls. DISCUSSION: This systematic review aims to synthesize the world's literature on the effects of hypercapnia in the setting of sepsis. We expect this systematic review will find that majority of the studies will demonstrate a potential benefit of higher PaCO2 levels in sepsis. The results of this systematic review will contribute to the understanding of the effects of hypercapnia in the setting of sepsis and promote future research of PaCO2 management in mechanically ventilated patients with sepsis. SYSTEMATIC REVIEW REGISTRATION: The systematic review is registered in the PROSPERO international prospective register of systematic review (PROSPERO # CRD42018086703 ).

Curricula and methods for physician compassion training: protocol for a systematic review.

INTRODUCTION: Compassionate patient care has been associated with improved clinical outcomes for patients. However, current evidence suggests that healthcare is experiencing a compassion crisis, with physicians frequently overlooking opportunities to treat patients with compassion. Although there is evidence that compassionate care can be enhanced through training interventions, it is currently unclear what specific skills and behaviours ought to be taught and how best to transfer this information to the learner. The objectives of this systematic review are to collate the world's literature on compassion training to determine (1) the specific skills and behaviours that should be taught (curriculum), and (2) the methods of training that are most effective at improving compassionate patient care. METHODS AND ANALYSIS: We will perform a qualitative systematic review of studies aimed at improving compassionate patient care among physicians and physicians in training. We will comprehensively search CENTRAL, MEDLINE, EMBASE and CINAHL. Additional recommended techniques for systematic reviews of complex evidence will be performed including pursuing selected 'references of references', electronic citation tracking and consulting experts in the field. Two investigators will independently review all search results. After identification and inclusion of papers, we will use a standardised form for data extraction. We will use tables to describe the study populations, interventions tested (including specific skill/behaviours taught and training methods used), outcome measures and effects of interventions on outcome measures compared with control groups. Where appropriate, meta-analysis will be used for quantitative analysis of the data. ETHICS AND DISSEMINATION: The proposed systematic review does not require ethical approval since no individual patient-level data will be collected. Results of this study will contribute to the understanding of compassion training and help inform the development of compassion training curricula. PROSPERO REGISTRATION NUMBER: CRD42018095040.